High impact information on a1-a

• The vitellogenin genes A1 and A2, in hepatocytes simultaneously expressed upon estrogen treatment, are heavily methylated in all adult tissues, irrespective of expression [1].
• The appearance of this high density peak of lysosomal enzyme activity coincides with the time of onset of vitellogenin endocytosis during oocyte development [2].
• An unusual lysosome compartment involved in vitellogenin endocytosis by Xenopus oocytes [2].
• Using cloned cDNAs to albumin, globin and vitellogenin mRNAs as hybridization probes, and heparin as an inhibitor of initiation of transcription, run-on assays with nuclei faithfully reproduced the transcriptional status of these genes in vivo [3].
• The data suggest that endocytic vesicles that contain vitellogenin fuse with modified lysosomes shortly after their internalization by the oocyte [2].

Biological context of a1-a

• The rate at which receptor binds estradiol explains the kinetics of the induction of vitellogenin synthesis by estradiol, and the dissociation constant (0.5 X 10(-9) M) explains the concentration dependence of the response, which has a threshold of 10(-9) M estradiol, when 67% of the receptor is bound to estradiol [4].
• We have investigated the effect of heat shock on primary cultures of male and female Xenopus laevis hepatocytes as a function of estrogen-induced vitellogenin gene expression [5].
• In contrast to the vitellogenin and retinol binding protein genes whose transcription is induced by estrogen in Xenopus liver, the runoff transcription rate of HMG-CoA reductase does not increase significantly on administration of estradiol-17 beta [6].
• Persistence, methylation and expression of vitellogenin gene derivatives after injection into fertilized eggs of Xenopus laevis [7].
• Using restriction fragment length polymorphism (RFLP) we have analyzed the segregation of alleles of the different vitellogenin genes of Xenopus laevis [8].

Anatomical context of a1-a

• We have used ammonium sulphate precipitation followed by affinity chromatography to partially purify the estrogen receptor from Xenopus laevis liver which may control the genes for vitellogenin, the precursor of the egg yolk proteins [4].
• We have investigated the lysosomal compartment of Xenopus oocytes to determine the possible role of this organelle in the endocytic pathway of the yolk protein precursor, vitellogenin [2].
• We recently showed that vigilin is the estrogen-inducible protein in polysome extracts which binds specifically to a segment of the 3' untranslated region (UTR) of estrogen-stabilized vitellogenin mRNA [9].
• We report the fate of different derivatives of the vitellogenin genes after injection into fertilized eggs of Xenopus [7].
• Vitellogenin sequences were rendered selectively more sensitive to limited DNAase-I digestion (15-20% of DNA rendered acid-soluble) during primary hormonal activation (5 days) of vitellogenin genes in liver, but not erythrocyte, nuclei [10].

Associations of a1-a with chemical compounds

• Vitellogenin mRNA accumulated for only 12 h after a single addition of 10(-6) M estradiol to male hepatocyte cultures; mestranol, but not 17 alpha-ethinylestradiol or diethylstilbestrol, was more potent than the natural hormone [11].
• The level and rate of accumulation of vitellogenin mRNA were 5-15 times higher in female than in male hepatocytes, mestranol and estradiol being more potent than 17 alpha-ethinylestradiol and diethylstilbestrol [11].
• Consistent with the conclusions drawn from the teratology which chelating agents induce in frog embryos (1), metal analysis shows that vitellogenin is a zinc protein with 1 g atom zinc/220 kDa monomer but containing no other IIB and transition metals [12].
• In addition, primary treatment with the antiestrogen tamoxifen prevents both receptor up-regulation and an enhanced rate of transcription or accumulation of vitellogenin mRNA on secondary hormonal exposure [13].
• Addition of cycloheximide to cell cultures during primary estrogen treatment abolishes both receptor up-regulation and increased rate of vitellogenin gene transcription on secondary stimulation [13].

Other interactions of a1-a

• 6. The specific activity of ovary cathepsin D was five to six times lower than that of the liver enzyme, as measured by hemoglobin-hydrolysis at pH 3, but the ovary enzyme was shown to be superior to the liver enzyme in terms of vitellogenin-cleaving activity, as examined at pH 5 [14].

Analytical, diagnostic and therapeutic context of a1-a

• N-terminal sequence analysis and SDS-PAGE demonstrated the presence of two forms of vitellogenin (A and B) [12].
• The VTG assay based on enzyme-linked immunosorbent assay (ELISA) has been widely used for many fish species to screen estrogenic and anti-estrogenic activities of chemicals and sewage effluents using immature fish and/or male fish [15].
• Northern blot hybridisation of liver RNA from oestrogen-treated males and females, probed with cloned vitellogenin cDNA, revealed the presence of mRNA of the same size in the three species of Xenopus, which was absent in untreated male liver [16].

References